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Br J Pharmacol. 2010 Jan;159(1):122-8. doi: 10.1111/j.1476-5381.2009.00521.x. Epub 2009 Dec 4.

Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT1A receptors.

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  • 1Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.

Abstract

BACKGROUND AND PURPOSE:

Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that induces anxiolytic- and antipsychotic-like effects in animal models. Effects of CBD may be mediated by the activation of 5-HT(1A) receptors. As 5-HT(1A) receptor activation may induce antidepressant-like effects, the aim of this work was to test the hypothesis that CBD would have antidepressant-like activity in mice as assessed by the forced swimming test. We also investigated if these responses depended on the activation of 5-HT(1A) receptors and on hippocampal expression of brain-derived neurotrophic factor (BDNF).

EXPERIMENTAL APPROACH:

Male Swiss mice were given (i.p.) CBD (3, 10, 30, 100 mg*kg(-1)), imipramine (30 mg*kg(-1)) or vehicle and were submitted to the forced swimming test or to an open field arena, 30 min later. An additional group received WAY100635 (0.1 mg*kg(-1), i.p.), a 5-HT(1A) receptor antagonist, before CBD (30 mg*kg(-1)) and assessment by the forced swimming test. BDNF protein levels were measured in the hippocampus of another group of mice treated with CBD (30 mg*kg(-1)) and submitted to the forced swimming test.

KEY RESULTS:

CBD (30 mg*kg(-1)) treatment reduced immobility time in the forced swimming test, as did the prototype antidepressant imipramine, without changing exploratory behaviour in the open field arena. WAY100635 pretreatment blocked CBD-induced effect in the forced swimming test. CBD (30 mg*kg(-1)) treatment did not change hippocampal BDNF levels.

CONCLUSION AND IMPLICATIONS:

CBD induces antidepressant-like effects comparable to those of imipramine. These effects of CBD were probably mediated by activation of 5-HT(1A) receptors.

PMID:
20002102
[PubMed - indexed for MEDLINE]
PMCID:
PMC2823358
Free PMC Article
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